Constitutive HIF-1α expression blunts the beneficial effects of cardiosphere-derived cell therapy in the heart by altering paracrine factor balance.
Constitutive HIF-1α expression blunts the beneficial effects of cardiosphere-derived cell therapy in the heart by altering paracrine factor balance.
复制标题
组成型HIF-1α表达通过改变旁分泌因子平衡，将心圈衍生的细胞疗法在心脏中的有益作用。
DOI：
10.1007/s12265-011-9265-3
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发表时间：
2011-06
影响因子：
3.4
通讯作者：
Abraham, Maria Roselle
中科院分区：
文献类型：
--
作者：
Bonios, Michael;Chang, Connie Yachan;Terrovitis, John;Pinheiro, Aurelio;Barth, Andreas;Dong, Peihong;Santaularia, Miguel;Foster, D. Brian;Raman, Venu;Abraham, Theodore P.;Abraham, Maria Roselle
关键词：
缺氧诱导因子-1 α（HIF-1α）的表达促进血管生成并影响干细胞的植入。我们研究了稳定过表达组成型活性HIF-1α对心球衍生细胞（CDC）植入和左心室功能的影响。用表达人HIF-1α组成型活性突变体（LVHIF-1α）的慢病毒转导CDC。将200万只雄性大鼠CDC注射到结扎雌性同系大鼠中LAD后的梗死区。心肌梗死后1周和4周，通过超声心动图测量以下组的左心室射血分数（EF）和环向应变：PBS组（n=7）、CELL组（n=7）和CELL-HIF组（n=7）。采用定量PCR检测HIF-1α、VEGF、内皮素-1表达和CDC植入。30天时，CELL-HIF组EF无变化（p=NS），CELL组EF增加（p=0.025），PBS组EF减少（p=0.021），但植入率相似（2.4%±3.3% vs 1.7%± 0.8%，p=NS）。在CELL-HIF组中，梗死区域的平均周向应变没有变化，但在CELL组中有所改善（p=0.02）。与未转导的CDC相比，暴露于缺氧的HIF-CDC中的内皮素-1和VEGF表达更高。CDCs中HIF-1α的表达减弱了CDC移植的有益功能效应，提示旁分泌因子平衡可能在心脏再生中起重要作用。
Hypoxia-inducible factor-1alpha (HIF-1α) expression promotes angiogenesis and can influence stem cell engraftment. We investigated the effect of stable over-expression of constitutively active HIF-1α on cardiosphere-derived cell (CDC) engraftment and left ventricular function. CDCs were transduced with a lentivirus expressing a constitutively active mutant of human HIF-1α (LVHIF-1α). Two million male rat CDCs were injected into the infarct following ligation of the mid-LAD in female syngeneic rats. Left ventricular ejection fraction (EF) and circumferential strain were measured by echocardiography at 1 and 4 weeks post-MI in the following groups: PBS group (n=7), CELL group (n=7), and CELL-HIF group (n=7). HIF-1α, VEGF, endothelin-1 expression, and CDC engraftment were measured by quantitative PCR. At 30 days, EF was unchanged in the CELL-HIF group (p=NS), increased in the CELL group (p=0.025), and decreased in the PBS group (p=0.021), but engraftment was similar (2.4%±3.3% vs 1.7%±0.8%, p=NS). Mean circumferential strain of the infarcted region was unchanged in the CELL-HIF group, but improved in the CELL group (p=0.02). Endothelin-1 and VEGF expression were higher in HIF-CDCs exposed to hypoxia, compared with non-transduced CDCs. HIF-1α expression in CDCs blunted the beneficial functional effects of CDC transplantation, suggesting that paracrine factor balance may play an important role in cardiac regeneration.
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DOI：
10.1016/s1387-2656(05)11004-7
发表时间：
2005-01-01
期刊：
BIOTECHNOLOGY ANNUAL REVIEW, VOL 11
影响因子：
--
作者：
Berridge, MV;Herst, PM;Tan, AS
通讯作者：
Tan, AS
影响因子：
20.1
作者：
Kizana, Eddy;Chang, Connie Y.;Marban, Eduardo
通讯作者：
Marban, Eduardo
DOI：
10.1152/ajpheart.01176.2006
发表时间：
2007-06-01
影响因子：
4.8
作者：
Popovic, Zoran B.;Benejam, Carlos;Penn, Marc S.
通讯作者：
Penn, Marc S.
DOI：
10.1152/ajpendo.1997.273.5.e922
发表时间：
1997-11-01
影响因子：
5.1
作者：
Rebsamen, MC;Church, DJ;Lang, U
通讯作者：
Lang, U
DOI：
10.1073/pnas.0911921106
发表时间：
2009-12-01
影响因子：
11.1
作者：
Rey, Sergio;Lee, KangAe;Semenza, Gregg L.
通讯作者：
Semenza, Gregg L.